Prospective Trial for the Diagnosis and Treatment of Intracranial Germ Cell Tumors - Full Text View

Purpose

STUDY DESIGN:

Prospective, non-randomised multicentre study with patients stratified according to risk groups INVESTIGATIONAL MEDICINAL PRODUCTS The IMPs on this trial are Carboplatin, Cisplatin, Ifosfamide and Etoposide (as approved by German competent authority).

PRIMARY OBJECTIVES:

Germinoma

To maintain current high event-free survival (EFS) rates using a risk adapted approach
In localised germinoma: to omit whole brain and spinal irradiation by using combined treatment with standard chemotherapy and ventricular irradiation (+/- boosts)
In bifocal tumours (pineal + suprasellar): to treat as non-metastatic disease and to omit whole brain and spinal irradiation by using combined treatment with standard chemotherapy and ventricular irradiation (+/- boosts)
In metastatic disease: to maintain current excellent EFS in metastatic germinoma with craniospinal irradiation Malignant non-germinoma

To improve EFS:

by dose escalation of chemotherapy in patients identified as high risk at diagnosis ( age < 6 years and/or AFP serum / CSF > 1000 ng/ml)
by standardising the surgical approach for residual disease after treatment Teratoma
To register patients and collect data regarding diagnostics, treatment and outcome in order to develop future treatment strategies

SECONDARY OBJECTIVES:

Germinoma

To minimise long term effects of irradiation by sparing spinal and whole brain radiotherapy in non-metastatic disease Malignant non-germinoma
In standard risk to maintain EFS with chemotherapy and local irradiation Teratoma
To evaluate the influence of surgery and treatment on outcome to assist in the development of a fu-ture treatment strategy For all histological subtypes
To improve accuracy of diagnosis and staging in all registered patients
To standardise neurosurgical intervention
For all patients requiring biopsy or resection according to protocol guidelines, to collect and to store tumour material, and CSF where possible, for use in future biological studies.

ENDPOINTS / Criteria for evaluation:

Main end point

Event-free survival, defined as minimum time from the date of diagnosis to:

Death from any cause
Relapse
Progressive disease on therapy
Or second malignancy

Secondary end points

Overall survival, defined as time to death from any cause, measured from the date of diagnosis
Short and long term toxicity.

Condition	Intervention	Phase
Intracranial Germ Cell Tumors	Radiation: craniospinal irradiation Drug: Carboplatin, Etoposide, Ifosfamide Radiation: ventricular irradiation Drug: Cisplatin, etoposide, Ifosfamide (standard) Drug: Cisplatin, Etoposide, Ifosfamide (high dose) Radiation: focal irradiation	Phase 4


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	SIOP CNS GCT II: Prospective Trial for the Diagnosis and Treatment of Children, Adolescents and Young Adults With Intracranial Germ Cell Tumors

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Ifosfamide Cisplatin Etoposide Carboplatin Etoposide phosphate

U.S. FDA Resources

Further study details as provided by University Hospital Muenster:

Primary Outcome Measures:

survival [ Time Frame: 5 years event free survival ] [ Designated as safety issue: Yes ]
Survival rates in respect to applied treatment , according to Kaplan-Meier estimation , 5 years event free survival

Secondary Outcome Measures:

short and long term toxicity [ Time Frame: until 7 years after start of trial ] [ Designated as safety issue: Yes ]
toxicity of treatment will be assessed with CTC criteria, severe toxicity will be analysed by safety desk
overall survival [ Time Frame: 7 years after start of trial ] [ Designated as safety issue: Yes ]
Overall survival will be measured by Kaplan -Meier Estimation , 5 years overall survival


Estimated Enrollment:	400
Study Start Date:	October 2011
Estimated Study Completion Date:	October 2018
Estimated Primary Completion Date:	October 2018 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Germinoma metastatic • Metastatic or incompletely staged germinomas (± teratoma) Do not receive chemotherapy in this protocol Radiotherapy Metastatic or incompletely staged pure germinoma 24 Gy (15 fractions) to craniospinal axis with a 16 Gy (10 fraction) boost to tumour bed and any intracranial metastases and spinal deposits (total tumour dose 40 Gy) Metastatic germinoma plus teratoma (incompletely resected) 24 Gy (15 fractions) to craniospinal axis ; 30.4 Gy (19 fraction) boost to tumour bed and 16 Gy (10 frac-tion) boost to metastases (total tumour dose 54.4 Gy)	Radiation: craniospinal irradiation Metastatic or incompletely staged pure germinoma 24 Gy (15 fractions) to craniospinal axis with a 16 Gy (10 fraction) boost to tumour bed and any intracra-nial metastases and spinal deposits (total tumour dose 40 Gy) Metastatic germinoma plus teratoma (incompletely resected) 24 Gy (15 fractions) to craniospinal axis ; 30.4 Gy (19 fraction) boost to tumour bed and 16 Gy (10 frac-tion) boost to metastases (total tumour dose 54.4 Gy) Patients with metastastic non-germinomatous disease at diagnosis After Chemotherapy: 30 Gy (20 fractions) to cranio-spinal axis with 24 Gy (15 fraction) boosts to tumour site and any intracranial metastases (total tumour dose 54 Gy) and 20.8 Gy (13 fraction) boosts to spinal deposits (total dose 50.8 Gy)
germinoma non-metastatic Chemotherapy: • Non-metastatic fully staged germinoma (± teratoma) Two courses (1 and 3) of Etoposide and Carboplatin, alternating with two courses (2 and 4) of Etoposide and Ifosfamide Note: Bifocal germinoma (pineal+suprasellar) are treated as non-metastatic germinoma, if staging shows no additional dissemination Radiotherapy Non-metastatic pure germinoma in PR/SD After Chemotherapy: 24 Gy (15 fractions) to whole ventricles with a 16 Gy (10 fraction) boost to tumour bed (total tumour dose 40 Gy) Non-metastatic germinoma in CR After Chemotherapy: 24 Gy (15 fractions) to whole ventricles Non-metastatic germinoma plus teratoma (incompletely resected) After Chemotherapy: 24 Gy (15 fractions) to whole ventricles; 30.4 Gy (19 fraction) boost to tumour bed (total tumour dose 54.4 Gy)	Drug: Carboplatin, Etoposide, Ifosfamide • Non-metastatic fully staged germinoma (± teratoma) Two courses (1 and 3) of Etoposide and Carboplatin, alternating with two courses (2 and 4) of Etoposide and Ifosfamide Radiation: ventricular irradiation Non-metastatic pure germinoma in PR/SD After Chemotherapy: 24 Gy (15 fractions) to whole ventricles with a 16 Gy (10 fraction) boost to tumour bed (total tumour dose 40 Gy) Non-metastatic germinoma in CR After Chemotherapy: 24 Gy (15 fractions) to whole ventricles Non-metastatic germinoma plus teratoma (incompletely resected) After Chemotherapy: 24 Gy (15 fractions) to whole ventricles; 30.4 Gy (19 fraction) boost to tumour bed (total tumour dose 54.4 Gy)
Non-germinoma non-metastatic standard risk Chemotherapy: • Standard risk non-germinomatous malignant GCT Four courses of Etoposide, Cisplatin and Ifosfamide (standard treatment ) After Chemotherapy: 54 Gy focal radiotherapy in 30 fractions	Drug: Cisplatin, etoposide, Ifosfamide (standard) Four courses of Etoposide, Cisplatin and Ifosfamide (standard treatment ) Radiation: focal irradiation • Patients with localised non-germinomatous disease at diagnosis After Chemotherapy: 54 Gy focal radiotherapy in 30 fractions
Non-Germinoma metastatic standard risk Chemotherapy Four courses of Etoposide, Cisplatin and Ifosfamide (standard treatment ) Radiotherapy After Chemotherapy: 30 Gy (20 fractions) to craniospinal axis with 24 Gy (15 fraction) boosts to tumour site and any intracranial metastases (total tumour dose 54 Gy) and 20.8 Gy (13 fraction) boosts to spinal deposits (total dose 50.8 Gy)	Radiation: craniospinal irradiation Metastatic or incompletely staged pure germinoma 24 Gy (15 fractions) to craniospinal axis with a 16 Gy (10 fraction) boost to tumour bed and any intracra-nial metastases and spinal deposits (total tumour dose 40 Gy) Metastatic germinoma plus teratoma (incompletely resected) 24 Gy (15 fractions) to craniospinal axis ; 30.4 Gy (19 fraction) boost to tumour bed and 16 Gy (10 frac-tion) boost to metastases (total tumour dose 54.4 Gy) Patients with metastastic non-germinomatous disease at diagnosis After Chemotherapy: 30 Gy (20 fractions) to cranio-spinal axis with 24 Gy (15 fraction) boosts to tumour site and any intracranial metastases (total tumour dose 54 Gy) and 20.8 Gy (13 fraction) boosts to spinal deposits (total dose 50.8 Gy) Drug: Cisplatin, etoposide, Ifosfamide (standard) Four courses of Etoposide, Cisplatin and Ifosfamide (standard treatment )
Non-germinoma non-metastatic high risk Chemotherapy Two courses of standard Etoposide, Cisplatin and Ifosfamide, followed by two dose intensified courses of Etoposide, Cisplatin and Ifosfamide with stem cell support Radiotherapy After Chemotherapy: 54 Gy focal radiotherapy in 30 fractions	Drug: Cisplatin, Etoposide, Ifosfamide (high dose) Two courses of standard Etoposide, Cisplatin and Ifosfamide, followed by two dose intensified courses of Etoposide, Cisplatin and Ifosfamide with stem cell support Radiation: focal irradiation • Patients with localised non-germinomatous disease at diagnosis After Chemotherapy: 54 Gy focal radiotherapy in 30 fractions
Non-Germinoma metastatic high risk Chemotherapy Two courses of standard Etoposide, Cisplatin and Ifosfamide, followed by two dose intensified courses of Etoposide, Cisplatin and Ifosfamide with stem cell support Radiotherapy After Chemotherapy: 30 Gy (20 fractions) to craniospinal axis with 24 Gy (15 fraction) boosts to tumour site and any intracranial metastases (total tumour dose 54 Gy) and 20.8 Gy (13 fraction) boosts to spinal deposits (total dose 50.8 Gy)	Radiation: craniospinal irradiation Metastatic or incompletely staged pure germinoma 24 Gy (15 fractions) to craniospinal axis with a 16 Gy (10 fraction) boost to tumour bed and any intracra-nial metastases and spinal deposits (total tumour dose 40 Gy) Metastatic germinoma plus teratoma (incompletely resected) 24 Gy (15 fractions) to craniospinal axis ; 30.4 Gy (19 fraction) boost to tumour bed and 16 Gy (10 frac-tion) boost to metastases (total tumour dose 54.4 Gy) Patients with metastastic non-germinomatous disease at diagnosis After Chemotherapy: 30 Gy (20 fractions) to cranio-spinal axis with 24 Gy (15 fraction) boosts to tumour site and any intracranial metastases (total tumour dose 54 Gy) and 20.8 Gy (13 fraction) boosts to spinal deposits (total dose 50.8 Gy) Drug: Cisplatin, Etoposide, Ifosfamide (high dose) Two courses of standard Etoposide, Cisplatin and Ifosfamide, followed by two dose intensified courses of Etoposide, Cisplatin and Ifosfamide with stem cell support
No Intervention: Teratoma collection of information on surgery, applied treatment and outcome

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Eligibility


Ages Eligible for Study:	Child, Adult, Senior
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Main residence in one of the participating countries
Primary diagnosis of an intracranial germ cell tumour
Written consent for trial participation, treatment according to the protocol and consent for data transfer

Exclusion Criteria:

Tumour entity other than primary intracranial germ cell tumour or CNS GCT as second malignancy
Primary diagnosis pre-dating the opening of SIOP CNS GCT II in the participating country of registration
Medical, psychiatric or social conditions incompatible with trial treatment or treatment according to protocol is not intended
Participation within a different trial for treatment of germ cell tumours and/or concurrent treatment within any other clinical trial. The only exceptions to this are trials with different endpoints, involving aspects of supportive treatment which can run parallel to SIOP CNS GCT II without influencing the outcome of this trial e.g. trials on antiemetics, antimycotics, antibiotics, strategies for psychosocial support etc.
Pregnancy and lactation
Any treatment not given according to protocol prior to registration

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01424839

Contacts


Contact: Gabriele Calaminus, MD	+492518358060	gabriele.calaminus@ukmuenster.de
Contact: Carmen Teske	+492518358055	carmen.teske@ukmuenster.de

Locations


Germany
University Hospital Muenster	Recruiting
Muenster, Germany, 48129
Contact: Gabriele Calaminus, MD +492518358060 gabriele.calaminus@ukmuenster.de
Contact: Carmen Teske +492518358055 carmen.teske@ukmuenster.de
Principal Investigator: Gabriele Calaminus, MD

Sponsors and Collaborators

University Hospital Muenster

Deutsche Kinderkrebsstiftung

Hannover Medical School

Gesellschaft fur Padiatrische Onkologie und Hamatologie - Germany

Investigators


Principal Investigator:	Gabriele Calaminus, MD	University Hospital Muenster

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site


Responsible Party:	University Hospital Muenster
ClinicalTrials.gov Identifier:	NCT01424839 History of Changes
Other Study ID Numbers:	UKM08_0057 2009-018072-33
Study First Received:	August 11, 2011
Last Updated:	June 3, 2015
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University Hospital Muenster:


SIOP CNS GCT II Patients with the primary disease of an Intracranial Germ Cell Tumors

Additional relevant MeSH terms:


Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Etoposide phosphate Isophosphamide mustard Cisplatin Carboplatin Etoposide Ifosfamide	Antineoplastic Agents Antineoplastic Agents, Phytogenic Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Alkylating Alkylating Agents

ClinicalTrials.gov processed this record on September 27, 2016

Prospective Trial for the Diagnosis and Treatment of Intracranial Germ Cell Tumors (SIOPCNSGCTII)